Removal of human ether-à-go-go related gene (hERG) K+ channel affinity through rigidity: a case of clofilium analogues

…, M Soethoudt, EB Lenselink, E Klaasse…

文献索引：Louvel, Julien; Carvalho, Joao F.S.; Yu, Zhiyi; Soethoudt, Marjolein; Lenselink, Eelke B.; Klaasse, Elisabeth; Brussee, Johannes; Ijzerman, Adriaan P. Journal of Medicinal Chemistry, 2013 , vol. 56, # 23 p. 9427 - 9440

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被引用次数: 7

摘要

Cardiotoxicity is a side effect that plagues modern drug design and is very often due to the off-target blockade of the human ether-à-go-go related gene (hERG) potassium channel. To better understand the structural determinants of this blockade, we designed and synthesized a series of 40 derivatives of clofilium, a class III antiarrhythmic agent. These were evaluated in radioligand binding and patch-clamp assays to establish structure–affinity relationships ...